Project Summary/Abstract Objective: The Supervising Hub (SH) at the Medical College of Wisconsin (MCW), in collaboration with 5 Spokes of our NINDS-funded Mid-America CTSA Consortium (MACC) SIREN Network, (Parkland Memorial Hospital (PMH) at the University of Texas Southwestern Medical Center and Methodist Hospital Spoke (MH), Indiana University, and 3 Chicago Spokes participating in one or more ED SIREN trials (Northwestern Memorial Hospital Spoke [NMH], University of Chicago Medical Center Spoke [UCMC], and the University of Illinois Hospital Spoke [UIH]) are submitting this application in response to RFA-NS-19-036 for consideration of becoming a Specialized Clinical Center (SCC) for the HEAL Initiative: Early Phase Pain Investigation Clinical Network (EPPIC-Net), hereafter known as MACC/EPPIC-Net. We have capitalized on our established MACC Hub and Spoke clinical research infrastructure and proven patient accrual/clinical trials performance while expanding access to patients with pain conditions and assembling an accomplished group of investigators with pain expertise to maximally support achievement of EPPIC-Net research goals. Methods: MACC/EPPIC-Net has been strategically assembled to efficiently and maximally support EPPIC-Net patient accrual. With a catchment of 9,931,00 people, long-standing multi-disciplinary collaboration, and expansion site capacity, MACC has the infrastructure to significantly contribute to patient accrual and the inherent flexibility to support any EPPIC-Net study. MACC/EPPIC-Net pain resources include 28 pain clinics, 10 accomplished pain researchers specializing in emergency medicine, toxicology, hematology, and oncology, board certified in pain medicine, transfusion medicine, addiction medicine, and toxicology, and access to 67,077 patients with low back pain/year and a total of 315,961 patients/year with painful conditions. We capitalize on standing infrastructure of 37 research personnel, with 24/7 coverage in place or planned at all sites. All sites have agreed to and routinely use Master Contract Agreements as well as central institutional review board review for trials. The Clinical and Translational Science Award (CTSA) Collaborative Council, consisting of the local CTSA PI at each MACC/EPPIC-Net site, will support EPPIC-Net trials. Specific Aims. MACC/EPPIC-Net aims to: 1) Leverage our infrastructure, collaboration and experience to achieve rapid and exemplary execution of Phase 2 clinical trials in patients with well-defined pain conditions to test novel drugs, biologics and devices, meeting or exceeding the recruitment goals and study milestones for EPPIC-Net, 2) Engage a wide spectrum of investigators with expertise in anesthesia, emergency medicine, neurology, rheumatology, obstetrics/ gynecology, oncology, orthopedics, gastroenterology and other subspecialties, 3) Capitalize on the scientific expertise of MACC/EPPIC-Net to develop novel, Phase 2 clinical protocols, stimulate independent EPPIC-Net grant applications, and significantly contribute to EPPIC-Net governance committees, and 4) Utilize national leadership positions of MACC/EPPIC-Net investigators to promote dissemination of EPPIC-Net study findings.